Equipment supplement to "Training Innate Immunity: A new approach to the treatment of sepsis"

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Abstract Sepsis is the leading cause of death in non-cardiac intensive care units (ICU) and accounts for 40% of ICU expenditures. Patients that survive sepsis have long term physical and cognitive disabilities and are frequently readmitted to the hospital with recurrent infections. Over the past two decades there has been an increased incidence of sepsis and this trend is likely to continue due to our aging population, increased use of immunosuppressive drugs and invasive procedures and the emergence of antibiotic resistant opportunistic pathogens. Attempts at developing effective therapies to prevent or treat sepsis have proven to be exceedingly difficult. No drugs are currently approved by the FDA for the treatment of sepsis. It is clear that new approaches for the prevention and treatment of sepsis are needed. In the parent award (RO1GM119197), we proposed the novel concept that it is possible to “train” the innate immune system to facilitate a more effective response to existing and secondary infections. In this research, we utilize β-glucan isolated from C. albicans to induce trained immunity. The β-glucan reagent is prepared in the PIs (Williams) laboratory and it is the immune training reagent used for the experiments detailed in the parent award at both ETSU (Williams) and Vanderbilt (Sherwood). In fact, the Williams laboratory is the “sole source” of the β-glucan immune training reagent which is employed in the parent award. The isolation and quality control of β-glucan is a multi-step process, which requires chromatographic purification at the preparative level in order to obtain a high purity, i.e. >95%, β- glucan reagent in quantities sufficient for the experiments being done at both ETSU and Vanderbilt. Our current preparative chromatography system is twenty years old. It is currently not operational and must be replaced. This supplement requests an Agilent 1260 Infinity II preparative chromatography system. The Agilent 1260 system is a high performance, fully automated preparative chromatography system with multiple detectors that will enable us to isolate and purify sufficient quantities of -glucan in order to complete the specific aims of our parent award.